A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE

NCT00914966 | Completed Phase 4 Results

• 2 other identifiers: 0624-400SHP616-400
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 11

Brief Summary

The objectives of the study were:

1. 1.To assess the safety and tolerability of escalating doses of CINRYZE.
2. 2.To assess the effect of an escalating dose algorithm for CINRYZE on hereditary angioedema (HAE) attack rates.
3. 3.To assess the immunogenicity of CINRYZE.

Conditions

Hereditary Angioedema

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Adverse Events, Hospitalizations, Thrombotic Events, Treatment-emergent C1 INH Antibodies, Post-baseline Toxicity Grade Increases in Clinical Laboratory Parameters, and Post-dose Vital Signs Changes of Potential Clinical Importance

  Events reported during the 3 month follow-up period are counted with the dose level at which they occurred.

  12 to 24 weeks at each dose level

Secondary Outcomes (1)

• Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates

  12 weeks at each dose level

Study Arms (1)

CINRYZE

EXPERIMENTAL

There were 3 potential dose escalation steps: * Step 1: 1500 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks * Step 2: 2000 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks * Step 3: 2500 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks

Biological: C1 inhibitor (human) [C1 INH]

Interventions

C1 inhibitor (human) [C1 INH] BIOLOGICAL

Also known as: CINRYZE, C1 esterase inhibitor (human)

CINRYZE

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible for this protocol, subjects must:
• Be ≥6 years of age and ≥25 kg body weight.
• Have a confirmed diagnosis of HAE with a documented history of swelling of the face, extremities, gastrointestinal tract, genitalia, or larynx and a history of at least one of the following:
• C1 INH gene mutation
• C4 level below the lower limit of the reference range
• C1 INH antigen level below the lower limit of the reference range
• Functional C1 INH level below the lower limit of the reference range
• Family history of HAE (i.e., grandparent, parent, sibling)
• Have a history of \>1.0 HAE attack per month (average) of any severity during the 3 consecutive months prior to screening while receiving the recommended CINRYZE dosing of 1000 Units every 3 to 4 days via intravenous injection.
• If an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
• If a child, have a parent/legal guardian who is willing and able to provide written informed consent for the child to participate in the study (with assent from the child when appropriate).

You may not qualify if:

• To be eligible for this protocol, subjects must not:
• Have, as determined by the investigator and/or the sponsor's medical monitor, any surgical or medical condition that could interfere with the administration of study drug or interpretation of study results.
• Have a history of abnormal blood clotting or other coagulopathy.
• Be taking prescription anticoagulant medication.
• Have a history of allergic reaction to CINRYZE or other blood products.
• Have participated in any other investigational drug study within the past 30 days (other than CINRYZE protocols).
• Have received any blood products (other than CINRYZE) within 60 days prior to screening.
• Have any of the following laboratory values at screening:
• Hemoglobin \<8 g/dL
• White blood cell count \<2 x 10\^9/L or \>20 x 10\^9/L
• Platelet count \<50 x 10\^9/L or \>400 x 10\^9/L
• Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>2.0 x the upper limit of normal
• Blood urea nitrogen and/or creatinine \>2.0 x the upper limit of normal
• Be pregnant or breastfeeding.

Sponsors & Collaborators

• Shire: lead

Study Sites (11)

Allergy, Asthma and Immunology Associates

Scottsdale, Arizona, 85251, United States

Location

Family Allergy and Asthma Center

Atlanta, Georgia, 30342, United States

Location

Institute for Asthma and Allergy

Wheaton, Maryland, 20902, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Allergy and Asthma Research Group

Eugene, Oregon, 97401, United States

Location

Baker Allergy, Asthma and Dermatology Research Center

Lake Oswego, Oregon, 97035, United States

Location

East Tennessee Center for Clinical Research

Knoxville, Tennessee, 37909, United States

Location

Unknown Facility

Bryan, Texas, 77802, United States

Location

AARA Research Center

Dallas, Texas, 75231, United States

Location

Marycliff Allergy Specialist

Spokane, Washington, 99204, United States

Location

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

Complement C1 Inhibitor Protein; SERPING1 protein, human

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Complement Inactivator Proteins; Complement System Proteins; Immunoproteins; Blood Proteins; Proteins

Limitations and Caveats

Per Changes in the Planned Analyses: The clinical presentation of disease manifestations and response to therapy are highly variable among patients with HAE and as such, the efficacy results from this study are presented in this report by individual participant in narrative summaries rather than as summary statistics. Thus, one outcome measure (Use of rescue therapy and/or other therapy for treatment of HAE symptoms) is not presented.

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2009
• First Posted: June 5, 2009
• Study Start: August 31, 2009
• Primary Completion: May 24, 2012
• Study Completion: May 24, 2012
• Last Updated: June 23, 2021
• Results First Posted: July 18, 2013

Record last verified: 2021-06

Locations

US (11)